This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite the widespread use of highly active antiretroviral therapy (HAART), neurological disorders continue to contribute significantly to the morbidity and mortality associated with HIV infection. The immunological correlates of protection against HIV encephalitis (HIVE) have not been identified;however, this information is critical for designing AIDS vaccines that are capable of safely suppressing viral replication in the brain as well as in peripheral lymphoid tissues. Although little is known about the specific effect of antiviral antibodies on the course of HIV neuropathogenesis, recent reports suggest that patients with impaired neutralizing antibody (NAb) responses may be at increased risk for the development of HIV-associated dementia (HAD). In this research program we are using a neurovirulent SIV/macaque model to investigate the role of adaptive host immunity in providing protection against the development of SIV encephalitis (SIVE). The central hypothesis of this project argues that NAb are important for providing collateral protection against the development of SIVE in animals with suboptimal cell-mediated immune responses.